903565-83-3

Usage

Uses

Used in Pharmaceutical Industry:
Tofogliflozin is used as an antidiabetic medication for improving glycemic control in diabetic patients. It works by inhibiting the SGLT2 protein, which helps to reduce glucose reabsorption in the kidneys and promote its excretion through urine, leading to a decrease in blood glucose levels.

Upstream product

• 903566-45-0 C₅₀H₅₀O₇ 
• 903566-43-8 C₄₂H₄₂O₇ 
• 903566-44-9 (1S,3'R,4'S,5'R,6'R)-3',4',5'-tris(benzyloxy)-6′-((benzyloxy)-methyl)-3′,4′,5′,6′-tetrahydro-3H-spiro[2-benzofuran-1,2′-pyran]-6-carbaldehyde 
• 89980-92-7 (2-bromo-1,4-phenylene) dimethyl carbinol 
• 1019209-73-4 2-bromo-1,4-bis(((2-methoxypropan-2-yl)oxy)methyl)benzene 
• 903566-65-4 (1S,3′R,4′S,5′S,6′R)-3′,4′,5′,6′-tetrahydro-6,6′-bis(hydroxymethyl)spiro[2-benzofuran-1(3H),2-[2H]pyran]-3′,4′,5′-triol 
• 90-80-2 D-Glucono-1,5-lactone 
• 1201913-74-7 (1S,3'R,4'S,5'R,6'R)-6-(4-ethylbenzyl)-6′-((pivaloyloxy)-methyl)-3',4',5',6'-tetrahydro-3H-spiro[isobenzofuran-1,2'-pyran]-3',4',5'-triyl tris(2,2-dimethylpropanoate) 
• 18643-86-2 dimethyl 2-bromoterephthalate 
• 586-35-6 2-bromo-1,4-benzenedicarboxylic acid 
• 1426923-29-6 (3'R,4'S,5'R,6'R)-3',4',5'-tris(benzyloxy)-6'-(benzyloxymethyl)-5-chloro-6-(4-ethylbenzyl)-3',4',5',6'-tetrahydro-3H-spiro[isobenzofuran-1,2'-pyran] 

Relevant academic research and scientific papers

Synthesis of Tofogliflozin as an SGLT2 Inhibitor via Construction of Dihydroisobenzofuran by Intramolecular [4 + 2] Cycloaddition

The synthesis of tofogliflozin (1), a sodium glucose cotransporter 2 (SGLT2) inhibitor, was achieved through the key steps of intramolecular [4 + 2] cycloaddition of dienone-yne intermediate, aerobic aromatization, and anomeric equilibration, thus enablin

The regioselective bromine-lithium exchange reaction of alkoxymethyldibromobenzene: A new strategy for the synthesis of tofogliflozin as a SGLT2 inhibitor for the treatment of diabetes

The regioselective bromine-lithium exchange reaction of 2,4-dibromo-1-(1-methoxy-1-methylethoxymethyl)benzene (2), which resulted in optimized selectivity of 220:1, is described. Applying this method to the synthesis of tofogliflozin (1) as a SGLT2 inhibi

Preparation method of Tofogliflozin monohydrate

The invention relates to a preparation method of Tofogliflozin monohydrate. In the route, p-Hydroxybenzoic acid used as a starting material is subjected to acylation, iodination, Friedel-Crafts and reduction reaction to obtain an iodinated diphenylmethane framework; by means of the characteristic that an iodinated substance is reactive, the splicing the diphenylmethane framework and a saccharide ring is realized under mild conditions through the effect of isopropyl magnesium chloride lithium chloride; and the eleven-step total yield is 22%. The route is high in yield, favorable in selectivity, low in production cost and mild in reaction conditions, does not use flammable, explosive or high-toxicity reagent, obtains products and intermediate compounds which are easy to purify, and is suitable for industrial production.

A Scalable Synthesis of Tofogliflozin Hydrate

A newly process for the synthesis of tofogliflozin hydrate, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, was described. Three improvements were achieved, including the development of a regioselective Friedel-Crafts reaction, a high-yield reduction, and a mild metal-halogen exchange. These improvements ultimately resulted in the isolation of tofogliflozin hydrate as a white solid in >99% purity (HPLC area) and 23% overall yield after 12 steps without column chromatography.

Development of a Scalable Synthesis of Tofogliflozin

An efficient and scalable synthesis of an antidiabetic drug, tofogliflozin (1), which was identified as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor, is described. A key factor in the synthesis of 1 was the selection of the purpose-designed protecting group, which plays a strategic role in protection, chemoselective activation, and crystalline purification. The developed and optimized method made it possible to prepare 1 on a multidecagram scale without any column chromatography.

Method for preparing derivatives of spiroketal

Provided is a process for the preparation of a spiroketal derivative via a compound represented by general formula (II) [wherein each variable group and each variable number are as defined in the description].

Improved preparation of (1S,3′R,4′S,5′S,6′R)-5- chloro-6-[(4-ethylphenyl)methyl]-3′,4′,5′,6′-tetrahydro- 6′-(hydroxymethyl)-spiro[isobenzofuran-1(3H),2′-[2H]pyran]-3′, 4′,5′-triol

A convenient approach for the preparation of (1S,3′R,4′S, 5′S,6′R)-5-chloro-6-[(4-ethylphenyl)methyl]-3′,4′, 5′,6′-tetrahydro-6′-(hydroxymethyl)-spiro[isobenzofuran-1(3H), 2′-[2H]pyran]-3′,4′,5′-triol is developed. The targeted compound was synthesized from 2-bromo-4-methylbenzoic acid in nine steps and the isomers of undesired ortho-products were avoided during the preparation.

Discovery of tofogliflozin, a novel C-arylglucoside with an O-spiroketal ring system, as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes

Inhibition of sodium glucose cotransporter 2 (SGLT2) has been proposed as a novel therapeutic approach to treat type 2 diabetes. In our efforts to discover novel inhibitors of SGLT2, we first generated a 3D pharmacophore model based on the superposition o

CRYSTAL OF SPIROKETAL DERIVATIVE, AND PROCESS FOR PRODUCTION THEREOF

The present invention provides a process for preparing a spiroketal derivative, via an intermediate represented by Formula (VI): wherein variable groups and numbers are as defined in the specification, which can be produced from dihalobenzene derivatives in one pot reaction.

SPIROKETAL DERIVATIVE AND USE THEREOF AS DIABETIC MEDICINE

The present invention provides a compound of Formula (I): wherein R1, R2, R3 and R4 are each independently selected from a hydrogen atom, an optionally substituted C1-C6 alkyl group, an opt